The Boxer dog is the sixth (out of 156 registered dog breeds) most popular registered dog breed in the United States. Unfortunately the Boxer is also the most commonly reported breed to be affected with the cardiac disease, arrhythmogenic right ventricular cardiomyopathy (ARVC) (Basso et al., Circulation, 109:1180-1185, 2004). Previously termed Boxer cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy in the Boxer dog is a familial disease that is inherited in an autosomal dominant pattern (Basso et al., Circulation, 109:1180-1185, 2004; Meurs et al., J Vet Intern Med, 13:437-439, 1999; Harpster, Boxer Cardiomyopathy, in Kirk R W, ed. Current Veterinary Therapy VIII Small Animal Practice; 329-337, 1983). Affected dogs suffer from rapid ventricular tachyarrhythmias that may lead to cardiac syncope or sudden cardiac death (FIG. 1). Postmortem evaluation includes the identification of unique histological fibrofatty replacement of myocardium in the right ventricle (and sometimes interventricular septum and left ventricle) (FIG. 2). The histopathological changes may lead to right, and sometimes left myocardial ventricular dysfunction. (Baumwart et al., J Vet Intern Med, 23:271-274, 2009).
Arrhythmogenic right ventricular cardiomyopathy is also a common cause of sudden cardiac death in human beings (Thiene et al., Orphanet J Rare Dis., 2:45, 2007). The disease in human beings is most commonly a familial disease associated with a causative mutation in a gene that encodes for a desmosomal (cell junction) protein (Id).
At this time there is no single test that provides a definitive diagnosis of ARVC in the Boxer dog. Instead, the diagnosis is defined by a combination of the following findings: post-mortem histological identification of fibrofatty replacement of myocardium in the right ventricle, ventricular tachyarrhythmias, syncope or exercise intolerance, and a history of familial disease (Basso et al., Circulation, 109:1180-1185, 2004; Harpster, Boxer Cardiomyopathy, in Kirk R W, ed. Current Veterinary Therapy VIII Small Animal Practice; 329-337, 1983). There is therefore a need to develop a test to definitively diagnose ARVC in Boxer dogs.